A recent report from three Scandinavian clinical trials evaluating tamoxifen therapy among breast cancer patients has raised concern that tamoxifen therapy could increase the risk of a subsequent colorectal malignancy. We propose to test the hypothesis that tamoxifen use among breast cancer patients is associated with an elevated risk of second primary colorectal cancer in a population-based study. The proposed study is a nested case-control investigation of new primary colon and retal cancers among women with a prior diagnosis of brest cancer. Women diagnosed with Stage I, II, or III breast cancer between January 1, 1978 and December 31, 1992 will be identified from the population-based Cancer Surveillance System (CSS) of western Washington. All women in the study cohort who are subsequently diagnosed with new primary colon or retal cancer as their secondary primary cancer at least six months following the unilateral diagnosis and before December 31, 1994 will be study cases (total, n=161). For each case, we will identify at least two controls from the study cohort matched on the following characteristics of the case at the time of unilateral diagnosis: calendar year, age (in 5 year age groups), stage of disease (I,II, or III) (n=361). Tamoxifen therapy and other study information, will be obtained by abstracting hospital medical records of cases and controls and through a self-administered questionnaire sent to physicians who were involved in each patients' care. Analyses will be conducted to compare the relative risk of colorectal cancer in relation to the duration and recency of tamoxifen use. The success of tamoxifen as a breast cancer therapy, coupled with the minimal short-term effects, has initiated interest in using tamoxifen prophylactically in primary prevention of breast cancer. It is reasonable to expect that long-term adverse effects will be accepted and tolerated by most breast cancer patients, since tamoxifen has demonstrated efficacy for this potentially life-threatening disease. Such effects may not be acceptable to healthy women, including those at higher than average risk for breast cancer. It is important to document all beneficial and adverse health effects associated with tamoxifen treatment so that an informed decision can be made with respect to the prophylactic use of the drug.